In this proposal we wish to examine the hypothesis that, as in other tissues, interaction of carcinogens with nuclear components occurs in the pancreas which results in altered regulatory and synthetic processes. These altered processes could eventually lead to pancreatic tumor formation. Recent evidence indicates there is an increasing incidence of pancreatic cancer. There is also a strong correlation between chemicals and tobacco tar products and tumor formation. There is little information in the literature concerned with nuclear events in the pancreas, and only a few reports describe effects of chemical carcinogens. It is the objective of this proposed research to study certain nuclear processes in pancreatic tissue following the administration of carcinogens that are known inducers of pancreatic tumors and to compare this response to that of liver and lungs. These processes will be studied in normal animals and animals that have been chronically stimulated to produce pancreatic hyperplasia, which may make the processes more susceptible to carcinogens. The events to be studied are: 1) binding of carcinogens to pancreatic macromolecules; 2) quantitative and qualitative histone and non-histone protein changes to include phosphorylation and acetylation of these fractions; 3) DNA-dependent RNA polymerase enzyme changes; 4) changes in template efficacy; 5) quantitative and qualitative changes in ribonucleic acids; 6) changes in RNA maturation and transport. Where a process is perturbed, we will continue observations until either the change ceases or transformation is detected. Four carcinogens will be employed: 7,12 dimethyl-benzanthracene, 3-4-benzo(a)pyrene, hydroxymethylnitrosourethane, and diisopropanol-nitrosamine. Except for benzopyrene, these carcinogens have been reported to produce pancreatic tumors. We hope to determine from these studies what nuclear processes are altered following carcinogen administration, whether the carcinogens have a common mode of action, and how these processes might relate to subsequent tumorigenic processes.